Interactions between dopamine (DA) and glutamate (GLU) in the mesocorticolimbic pathway of the brain may influence motivation and reward. Previous work from this laboratory has demonstrated that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor blockade may potentiate decreases in exploratory motor activity induced by the DA D(2/3) receptor agonist 7-OH-DPAT in the nucleus accumbens septi (NAS). This study investigated the interaction of AMPA/kainate receptor antagonists CNQX or NBQX with 7-OH-DPAT on ventral tegmental area (VTA) brain stimulation reward (BSR). Effects of these compounds, alone and combined, were measured in male Sprague-Dawley rats stereotaxically implanted with a unilateral VTA electrode and bilateral guide cannulae in the NAS core or shell subregions. Rate-frequency analysis was used to assess BSR frequency thresholds and maximum response rates of rats trained to lever-press for reinforcing electrical stimulation. When given alone, CNQX (0.5 microg), NBQX (0.5 microg), or 7-OH-DPAT (5.0 microg) did not affect BSR frequency thresholds. Co-administration of CNQX or NBQX with 7-OH-DPAT synergistically increased BSR frequency thresholds, indicative of decreased reward. These data indicate that simultaneous AMPA/kainate receptor blockade and DA D(2/3) receptor stimulation in the NAS may act synergistically to inhibit motivated behaviours such as electrical brain self-stimulation.